ABSTRACT
A new approach, SiteGA, for the prediction of functional transcription factor binding sites has been developed. The approach is based on the detection of locally positioned dinucleotides by the genetic algorithm and discriminant analysis. The approach has been applied to recognize transcription factor binding sites involved in the regulation of immune responses and cell growth (AP-1, IRF1, ISGF3, NFkappaB, STAT1), obesity and lipid metabolism (HNF4, PPAR, SREBP), and the expression of steroidogenesis genes (SF-1). SiteGA is far superior in accuracy to the traditionally used method of position weight matrices. The approach was implemented in the web tool, SiteGA http://wwwmgs2. bionet.nsc.ru/mgs/programs/sitega.
Subject(s)
Algorithms , DNA-Binding Proteins/genetics , Response Elements/genetics , Software , Transcription Factors/genetics , Animals , DNA-Binding Proteins/immunology , Humans , Immune System/physiology , Internet , Lipid Metabolism/genetics , Lipid Metabolism/immunology , Predictive Value of Tests , Protein Binding/genetics , Response Elements/immunology , Transcription Factors/immunologyABSTRACT
Development of methods for mathematical simulation of biological systems and building specific simulations is an important trend of bioinformatics development. Here we describe the method of generalized chemokinetic simulation generating flexible and adequate simulations of various biological systems. Adequate simulations of complex nonlinear gene networks--control system of cholesterol by synthesis in the cell and erythrocyte differentiation and maturation--are given as the examples. The simulations were expressed in terms of unit processes--biochemical reactions. Optimal sets of parameters were determined and the systems were numerically simulated under various conditions. The simulations allow us to study possible functional conditions of these gene networks, calculate consequences of mutations, and define optimal strategies for their correction including therapeutic ones. Graphical user interface for these simulations is available at http://wwwmgs.bionet.nsc.ru/systems/MGL/GeneNet/.
Subject(s)
Models, Genetic , Algorithms , Cholesterol/biosynthesis , Computer Graphics , Diploidy , Erythrocytes/metabolism , Haploidy , Internet , KineticsABSTRACT
A complex approach to recognize transcription factor binding sites (TFBS) has been developed based on four methods: (i) weight matrix, (ii) information content, (iii) multidimensional alignment, and (iv) pairwise alignment with the most similar representative of known sites. It has been shown that no method optimal for all kinds of sites occurs among the considered methods, so in each case, the appropriate way of recognition should be chosen. The approach proposed allows one to minimize the errors of TFBS recognition. The program available through the Internet (http://www.sgi.sscc.ru/mgs/programs/multalig/) has been created to search for the potential TFBS in nucleotide sequences set by the user.
Subject(s)
Databases, Nucleic Acid , Transcription Factors/metabolism , Base Sequence , Binding Sites , DNA , Internet , Promoter Regions, GeneticABSTRACT
The structure of the Transcription Regulatory Regions Database (TRRD) and the principles of considering transcription regulation of eukaryotic genes in TRRD are concerned. Formal description of the structural and functional organization of the regulatory gene regions is illustrated with examples. By now, TRRD is based on 3500 original works and contains data on transcription regulation of more than 1100 genes known to possess more than 5000 transcription factor-binding sites and about 1600 regulatory elements (promoters, enhancers, silencers). TRRD is available at http://www.bionet.nsc.ru/trrd/.
Subject(s)
Databases, Nucleic Acid , Eukaryotic Cells , Transcription, Genetic/genetics , Base Sequence , Regulatory Sequences, Nucleic AcidABSTRACT
A database for gene networks GeneNet was created. The main principles of formalized description of gene networks for the cases of regulation of antiviral responses and hemopoiesis were developed. A program for automatic graphical representation of diagrams of gene networks was created, which is based on their formalized description. A system of filters was developed, which makes it possible to select individual network components for graphical representation. The selection can be performed with respect to specific type of treatment, species, and/or cell type. The GeneNet database is accessible via Internet at http://wwwmgs.bionet.nsc.ru/systems/MGL/Gen eNet.
Subject(s)
Computer Graphics , Databases, Factual , Animals , Automation , Base Sequence , Hematopoiesis , Humans , Mice , Virus Diseases/immunologyABSTRACT
We have developed GeneExpress that is the WWW-oriented integrator for the databases and systems supporting the investigation of gene expression. The total number of the Web-based resources integrated is 30. The database GeneNet on molecular events forming gene networks was assigned its integrative core. To navigate all these WWW-available resources, the SRS, HTML, and Java viewers were developed, http:@wwwmgs.bionet.nsc.ru/systems/GeneExpress/.
Subject(s)
Database Management Systems , Gene Expression , Internet , Systems Integration , Programming LanguagesABSTRACT
gamma-p-Azidoanilidate of dTTP was used to study the photoaffinity modification of DNA polymerase I and Klenow fragment. The analog was found to be a mixed-type inhibitor with respect to dTTP of the polymerization reaction catalyzed by DNA polymerase I and Klenow fragment. In the absence of the reagent both UV-irradiated enzymes were rapidly inactivated. Substrates (dNTP and template-primer) protected the enzymes from inactivation by UV-light with different efficiency. In the presence of the template-primer UV-irradiation induced activation of DNA polymerase I. The effect of the analog on both enzyme forms under irradiation is different. At concentration of 10(-5)M gamma-p-anilidate of dTTP accelerated the activation of DNA polymerase I initiated by UV-irradiation and at 10(-4)M concentration it inactivated the enzyme by 20-25%. Under such conditions one enzyme molecule covalently bound two molecules of the analog. While the template-complementary substrate (dTTP) protected DNA polymerase I both from inactivation and modification, the non-complementary one (dCTP) worked only against modification. In contrast to DNA polymerase I Klenow fragment was not inactivated when exposed to UV-irradiation and gamma-p-anilidate of dTTP neither modified the protein nor exerted any significant effect on its polymerization activity. The data accumulated suggest the presence on the DNA polymerase I molecule of a regulatory region providing additional dNTP binding sites.
